Dioxin induces a novel nuclear factor, DIF‐3, that is implicated in spermatogenesis

Ohbayashi, Tetsuya; Oikawa, Kosuke; Iwata, Ryoko; Kameta, Akemi; Evine, Kazumi; Isobe, Toshiro; Matsuda, Yoichi; Mimura, Junsei; Fujii‐Kuriyama, Yoshiaki; Kuroda, Masahiko; Mukai, Kiyoshi

doi:10.1016/s0014-5793(01)03039-3

Cited by 30 publications

(34 citation statements)

References 22 publications

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“…Given that GGNBP2 is a conserved zinc finger protein in human and mouse,3, 4, 13 it presumptively has similar functions in regulation of spermatogenesis in humans. A recent comprehensive analysis revealed that sperm counts continually and significantly declined over a 38‐year period in men from Western countries 42.…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanism by which dioxins impair spermatogenesis remains elusive. The expression of GGNBP2 has been demonstrated to be regulated by dioxin and GGNBP2 plays critical roles in spermatocyte meiosis and spermatid differentiation 4, 13. Thereby, it would be worthwhile in future studies to investigate whether GGNBP2 is a factor that associates with dioxin‐induced reproductive toxicity by interfering with spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Ablation of Ggnbp2 impairs meiotic DNA double‐strand break repair during spermatogenesis in mice

Guo

Liu

et al. 2018

J Cellular Molecular Medi

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Gametogenetin (GGN) binding protein 2 (GGNBP2) is a zinc finger protein expressed abundantly in spermatocytes and spermatids. We previously discovered that Ggnbp2 resection caused metamorphotic defects during spermatid differentiation and resulted in an absence of mature spermatozoa in mice. However, whether GGNBP2 affects meiotic progression of spermatocytes remains to be established. In this study, flow cytometric analyses showed a decrease in haploid, while an increase in tetraploid spermatogenic cells in both 30‐ and 60‐day‐old Ggnbp2 knockout testes. In spread spermatocyte nuclei, Ggnbp2 loss increased DNA double‐strand breaks (DSB), compromised DSB repair and reduced crossovers. Further investigations demonstrated that GGNBP2 co‐immunoprecipitated with a testis‐enriched protein GGN1. Immunofluorescent staining revealed that both GGNBP2 and GGN1 had the same subcellular localizations in spermatocyte, spermatid and spermatozoa. Ggnbp2 loss suppressed Ggn expression and nuclear accumulation. Furthermore, deletion of either Ggnbp2 or Ggn in GC‐2spd cells inhibited their differentiation into haploid cells in vitro. Overexpression of Ggnbp2 in Ggnbp2 null but not in Ggn null GC‐2spd cells partially rescued the defect coinciding with a restoration of Ggn expression. Together, these data suggest that GGNBP2, likely mediated by its interaction with GGN1, plays a role in DSB repair during meiotic progression of spermatocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ablation of Ggnbp2 impairs meiotic DNA double‐strand break repair during spermatogenesis in mice

Guo

Liu

et al. 2018

J Cellular Molecular Medi

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“…The expression of several genes, such as wings apart-like (WAPL) [14] and dioxin inducible factor-3 (DIF-3) [20], are regulated by TCDD administration. We can evaluate the effects of TCDD on the reproductive system by using these genes as expression standards.…”

Section: Discussionmentioning

confidence: 99%

Maternal Exposure of Low Dose of TCDD Modulates the Expression of Estrogen Receptor Subunits of Male Gonads in Offspring

Ohyama

Ohta

Sano

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. We have analyzed the effects of low-dose transplacental and lactational exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression relating to the dioxin and sexual hormone cascade, and demonstrated the effects on testicular growth and sexual maturation in male offspring rats. TCDD (10 ng/kg) was administered to dams on Days 7 and 14 of gestation, and on Days 0, 7 and 14 after delivery. Gene expression of cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) in the liver of 17-day-old rats was significantly increased compared with controls. Furthermore, expression of estrogen receptors (ER)α and ERβ was significantly increased at 17 and 42 days old, respectively in the testis of TCDD-administered rats compared with controls. Although testicular weight and the seminiferous tubule diameter were increased in 17-day-old rats, there was no difference in the number of germ cells between TCDD-treated and control animals. The expressions of androgen receptor and inhibin subunit genes were not significantly changed. These findings suggest that low-dose exposure of TCDD leads to unusual development of the testis by perturbation of steroid hormone homeostasis.

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“…It is well known that TCDD mediates its toxicity by constructing an AhR (aryl hydrocarbon receptor) and Arnt (aryl hydrocarbon receptor nuclear translocator) [15,16] complex between TCDD, that binds to the XRE (xenobiotic responsive element) sequence, which is located upstream of the dioxinresponsive genes, such as cytochrome P450 gene family, whose expression it upregulates. Recently, the cDNA for DIF-3 (dioxin inducible factor-3), which has a zinc finger motif, was cloned from mouse testis, and the expression was induced by dioxin treatment [17]. This gene thus could be a candidate as a biomarker to assess the toxicity of dioxin for the reproductive system.…”

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confidence: 99%

A Novel Spermatogenesis Related Factor-2 (SRF-2) Gene Expression Affected by TCDD Treatment

et al. 2005

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Abstract. We have cloned a gene which is specifically expressed at the stage of sexual maturation in the rat testis by means of differential display, and have named it spermatogenesis-related factor-2 (SRF-2). Testicular expression was first detected at 5 weeks of age, and its level of the expression increased up to 7 weeks, and was maintained even at 63 weeks. Its cDNA was 2,789 bp in length and encoded an open reading frame of 718 amino acids. This gene was mainly expressed in the spermatocyte, judging from the result of in situ hybridization. The hypothetical gene product had a motif highly homologous with RabGAP/TBC protein. Taken together, this gene is considered to have some important functions for meiosis. The gene expression was significantly decreased by treatment with TCDD, a candidate endocrine disruptor, when administered to male rats of the nursling period. Body weight and testis weight were decreased by the treatment, but even then the sperm concentration in cauda epididymis was not changed significantly. SRF-2 gene may be a promising biomarker to construct a detection system of uncertain endocrine disruptors.

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Dioxin induces a novel nuclear factor, DIF‐3, that is implicated in spermatogenesis

Cited by 30 publications

References 22 publications

Ablation of Ggnbp2 impairs meiotic DNA double‐strand break repair during spermatogenesis in mice

Ablation of Ggnbp2 impairs meiotic DNA double‐strand break repair during spermatogenesis in mice

Maternal Exposure of Low Dose of TCDD Modulates the Expression of Estrogen Receptor Subunits of Male Gonads in Offspring

A Novel Spermatogenesis Related Factor-2 (SRF-2) Gene Expression Affected by TCDD Treatment

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